High levels of memory B cells are associated with response to a first tumor necrosis factor inhibitor in patients with rheumatoid arthritis in a longitudinal prospective study

Tumor necrosis factor inhibitor (TNFi) therapy is effective for rheumatoid arthritis (RA). Some reports suggested that the therapy affects B-cell homeostasis. We studied the effect of TNFi therapy on the distribution of peripheral B-cell subsets and elucidated B-cell-related biomarkers to predict the TNFi response. Peripheral B cells were analyzed for expression of CD19, CD27, CD38, and IgD in 31 healthy donors and 96 RA patients, including 21 who were followed 3 months after TNFi introduction. Treatment with steroids significantly altered the distribution of B-cell subsets. After adjustment for age, gender and steroid dose, patients with RA had similar B-cell subset proportions as controls. B-cell subset distribution did not differ by use of TNFi at baseline or before and after TNFi introduction. TNFi responders (according to European League Against Rheumatism criteria) at 3 months had significantly higher proportion of CD27+ memory B cells at baseline, and >= 26% CD27+ cells at inclusion was associated with a relative risk of 4.9 (1.3 to 18.6) of responding to TNFi treatment. CD27+ cells produced 3 times more TNFalpha than did naive B cells, and were correlated with interferon-gamma produced from CD4+ cells in patients without TNFi treatment. In patients with RA, high levels of baseline memory B cells were associated with response to TNFi, which may be related to TNFalpha-dependent activation of the T helper cell type 1 pathwa

Health-related quality of life among children with Turner syndrome: controlled cross-sectional study

International audienceBACKGROUND : The aim of the study was to assess health-related quality of life (HR-QoL) in children with Turner syndrome in comparison with controls.METHODS : We prospectively recruited 16 female girls with Turner syndrome (mean age 15.2±2.6 years) and 78 female controls (mean age 12.7±2.8 years) in randomly selected schools. We used the PedsQL, a generic HR-QoL questionnaire (self and parents' versions).RESULTS : Global HR-QoL scores in Turner syndrome were lower than controls for self-reports (respectively, 74.3±3.0 vs. 82.8±1.3, p=0.01) and parents' reports (62.7±3.8 vs. 80.1±1.7, p<0.0001). In Turner syndrome, self-reported HR-QoL was impaired in school functioning (70.6±4.0 vs. 80.71±1.7, p=0.02), social functioning (78.2±4.0 vs. 90.4±1.8, p<0.01) and physical functioning (78.5±3.2 vs. 87.1±1.4, p=0.02), but not in emotional functioning. Parents' reported HR-QoL was impaired in all four dimensions.CONCLUSIONS : HR-QoL was impaired in this cohort of young females with Turner syndrome, as in previously reported adult studies. In addition to medical treatment and routine clinical follow-up, female girls and teenagers with Turner syndrome should also be supported psychologically by social, educational and psychotherapeutic interventions that aim to address their self-esteem and emotional difficulties

Exposure to ambient air pollution and cognitive decline: Results of the prospective Three-City cohort study

BACKGROUND: Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive decline. However, there is still some heterogeneity in the findings, with inconsistent results depending on the pollutant and the cognitive domain considered. We wanted to determine whether air pollution was associated with global and domain-specific cognitive decline. METHODS: This analysis used data from the French Three-City prospective cohort (participants aged 65 and older at recruitment and followed for up to 12 years). A battery of cognitive tests was administered at baseline and every 2 years, to assess global cognition (Mini Mental State Examination, MMSE), visual memory (Benton Visual Retention Test), semantic fluency (Isaacs Set Test) and executive functions (Trail Making Tests A and B). Exposure to fine particulate matter (PM(2.5)), nitrogen dioxide (NO(2)) and black carbon (BC) at the participants' residential address during the 5 years before the baseline visit was estimated with land use regression models. Linear mixed models and latent process mixed models were used to assess the association of each pollutant with global and domain-specific cognitive decline. RESULTS: The participants' (n = 6380) median age was 73.4 years (IQR: 8.0), and 61.5% were women. At baseline, the median MMSE score was 28 (IQR: 3). Global cognition decline, assessed with the MMSE, was slightly accelerated among participants with higher PM(2.5) exposure: one IQR increment in PM(2.5) (1.5 µg/m(3)) was associated with accelerated decline (β: -0.0060 [-0.0112; -0.0007] standard unit per year). Other associations were inconsistent in direction, and of small magnitude. CONCLUSION: In this large population-based cohort, higher PM(2.5) exposure was associated with accelerated global cognition decline. We did not detect any significant association for the specific cognitive domains or the other pollutants. Evidence concerning PM(2.5) effects on cognition is growing, but more research is needed on other ambient air pollutants

Prevention of dementia : analysis of cognitive decline using a nonlinear model with latent process for longitudinal data.

Ce travail doctoral a pour premier objectif de replacer les démences dans leur contexte de santé publique en estimant des projections de nombre de cas de démences en France et en Europe jusqu'en 2050. La sensibilité de ces projections aux changements d'hypothèses sur les valeurs d'incidence ou de mortalité des sujets déments, sur le scenario démographique utilisé, et sur la mise en place d'une intervention de prévention, a également été évaluée. Dans ce contexte de forte augmentation du nombre de cas à venir, la prévention des démences, qu'elle soit primaire ou secondaire, sera amenée à tenir une place primordiale dans la prise en charge sociétale de ce problème. Pour pouvoir aboutir à des résultats, les recherches en prévention primaire et secondaire ont besoin de s'appuyer sur une méthodologie adaptée et de sélectionner des critères de jugements pertinents. Le déclin cognitif semble être un critère de jugement de choix, mais son l'utilisation doit éviter un certain nombre d'écueils et de biais. Nous avons dans un premier temps illustré l'analyse de ce critère dans le cadre d'un questionnement de prévention primaire à l'aide d'un modèle non linéaire à variable latente pour données longitudinales. Nous avons pour cela étudié la relation entre consommation chronique de benzodiazépines et déclin cognitif, et montré l'absence d'association sur un large échantillon. Dans un second temps nous avons utilisé ce type de modèle pour décrire et comparer les propriétés métrologiques d'un large ensemble de tests neuropsychologiques dans une cohorte clinique de sujets atteints de déficit cognitif modéré (MCI), et pour étudier la sensibilité de ces tests aux changements cognitifs lié aux prodromes de la maladie d'Alzheimer. Nos travaux ont ainsi permis de fournir des arguments permettant de sélectionner des tests neuropsychologiques susceptibles d'être utilisés dans le cadre de recherches de prévention secondaire pour identifier et/ou suivre les patients présentant un déficit cognitif modéré (MCI) lié à une maladie d'Alzheimer.The first aim of this doctoral work is to replace dementia in its public health context by estimating the number of dementia cases expected to occur in France and Europe over the next few decades until 2050. The sensitivity of these projections to hypotheses made on dementia incidence and mortality, demographic scenario used, and implementation of a prevention intervention, was also assessed. In this context of increasing number of future cases, the primary and secondary prevention of dementia will take a prominent place in the social management of this problem. Relevant research in the field of primary and secondary prevention requires an appropriate methodology and the use of relevant outcome. Cognitive decline seems to be an appropriate outcome, but a number of biases must be avoided. First, we illustrated the use of this criterion in the context of primary prevention using a nonlinear model with latent variable for longitudinal data to investigated the association between chronic use of benzodiazepines and cognitive decline. We showed the absence of association in a large population-based cohort. Secondly we used this model to describe and compare the metrological properties of a broad range of neuropsychological tests in a clinical cohort of patients with mild cognitive impairment (MCI). We also investigated the sensitivity of these tests to cognitive changes associated with prodromal Alzheimer's disease. Our work provides arguments for selecting neuropsychological tests which can be used in secondary prevention research, to identify and / or to follow patients with mild cognitive impairment (MCI) due to Alzheimer's disease

Consommation chronique de benzodiazépines et déclin cognitif chez le sujet âgé de plus de 65 ans

MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

How many dementia cases in France and Europe? Alternative projections and scenarios 2010-2050.

International audienceBACKGROUND AND PURPOSE: The objective of this study is to estimate the number of dementia cases expected to occur in France and Europe over the next few decades until 2050. METHODS: Our estimates are based on a model using the European incidence data for dementia by age and sex, the relative mortality risks related to dementia stratified by age classes, and the projections of mortality coefficients in the French and European general population. RESULTS: In France, in 2010, the number of dementia cases should reach 754000, i.e., 1.2% of the general population or 2.8% of the active population. By 2050 this number should be multiplied by 2.4, i.e., 1813000 cases, which will be 2.6% of the total population and 6.2% of the active population. In Europe this number could reach more than 6 millions in 2010 and 14 millions in 2050. The sensitivity analysis performed on French data showed that our projections were robust to the use of alternative data for incidence and relative mortality risk (variation of 5.5% and 6.5%), but very sensitive to hypotheses of evolution of mortality (variation of -22% to 29%). CONCLUSIONS: The approach used in our study, integrating both the dementia incidence and the mortality in the calculations, allowed us to refine the projections and stress the great sensitivity of the demographic hypotheses forecasts on the evolution of life expectancy. The likely increase is particularly important and confirms that French and European health systems must take this into account when making future plans

Persistence Analysis of Multi-scale Planar Structure Graph in Point Clouds

International audienceModern acquisition techniques generate detailed point clouds that sample complex geometries. For instance, we are able to produce millimeter-scale acquisition of whole buildings. Processing and exploring geometrical information within such point clouds requires scalability, robustness to acquisition defects and the ability to model shapes at different scales. In this work, we propose a new representation that enriches point clouds with a multi-scale planar structure graph. We define the graph nodes as regions computed with planar segmentations at increasing scales and the graph edges connect regions that are similar across scales. Connected components of the graph define the planar structures present in the point cloud within a scale interval. For instance, with this information, any point is associated to one or several planar structures existing at different scales. We then use topological data analysis to filter the graph and provide the most prominent planar structures. Our representation naturally encodes a large range of information. We show how to efficiently extract geometrical details (e.g. tiles of a roof), arrangements of simple shapes (e.g. steps and mean ramp of a staircase), and large-scale planar proxies (e.g. walls of a building) and present several interactive tools to visualize, select and reconstruct planar primitives directly from raw point clouds. The effectiveness of our approach is demonstrated by an extensive evaluation on a variety of input data, as well as by comparing against state-of-the-art techniques and by showing applications to polygonal mesh reconstruction

Multi-scale Planar Segments Extraction from Point Clouds

International audienceWe propose a flexible method to extract a set of segments from a 3D point cloud that are relevant across several scales and optimal in a planar sense. Since planar geometric primitives are ubiquitous, especially in man-made scene, their accurate detection is crucial for an abstract representation of point-based 3D data. In this paper, we introduce a new hierarchical graph representation in which each node represents a region at a given scale. The proposed graph is initialized with multiple segmentations performed at different scales and then reduced by collapsing groups of nodes. Each resulting group of nodes defines a meaningful segment and is obtained through an optimization that balances number of extracted segments and accuracy with respect to the input data in a planar sense. The output graph is a compact abstraction of the input cloud into multiple, possibly overlapping, segments, each relevant at a certain scale. The edges of the graph connect nodes whose segments overlap across different scales, thus allowing to represent both detailed and approximating parts of the scene

Body Composition in Individuals with Obesity According to Age and Sex: A Cross-Sectional Study

International audienceObesity is characterized by an alteration in body composition (BC); however, it is not known whether this alteration is modified by aging or sex. The aims of this study were to analyze BC in individuals with obesity based on age and sex and to determine the prevalence of sarcopenia. Seven hundred and fifty-five obese individuals were subdivided into four age groups. The hole (WB) and segmental BC were determined using dual-energy X-ray absorptiometry (DXA). In men, the WB lean tissue mass (LTM) and fat mass (FM) adjusted by weight and height were relatively constant with age. In women, the WBLTM was higher and WBFM was lower in the >65 group compared to the 18–34 group. A decrease in the LTM and FM at lower limbs and an increase in the trunk were observed, particularly in women, inducing a lower appendicular lean mass index (ALMI; appendicular LTM/height2) in the >65 group compared to the 18–34 group in both sexes. This study demonstrated that even though the WBLTM and FM are relatively constant with age, individuals with obesity present a localized redistribution of these two components. This body composition change leads to a decrease of the ALMI with age, one of the criteria included in the sarcopenia definitio

Comparison of the Lunar Prodigy and Stratos DR dual-energy X-ray absorptiometers to assess regional bone mineral density

International audienc